Since its first use in the retina in 1961, fluorescein angiography (FA) has been the gold standard for objective characterization of retinovascular disease (e.g. diabetic retinopathy, retinal vein occlusions, and choroidal neovascularization associated with age-related macular degeneration (AMD)). Despite its widespread use, FA is costly, invasive, and time consuming, limiting the usefulness as a screening tool. Optical coherence tomography (OCT) and its faster variation called spectral domain OCT (SDOCT) are interferometric imaging techniques which allow three-dimensional imaging of the retinal structure. This technique has enabled clinical imaging of retinal morphology and pathologic alteration with resolution nearly comparable to histologic sections. Because OCT is not capable of rendering most retinovascular abnormalities, it is frequently performed with FA to diagnose and manage patients with macular disease. As a potential alternative to FA in diagnosing retinovascular disease, we have developed an imaging method called phase contrast optical coherence tomography (PC-OCT) which uses specialized software analysis of data acquired from clinically available SDOCT imaging systems to provide the additional functionality of high resolution imaging of retinal vessels and choroidal neovascularization. To develop PC-OCT imaging as a non-invasive alternative for fluorescein angiography, we have the following goals: (1) improve the speed, accuracy and automation of PC-OCT imaging to allow for general clinical usage, and apply this developed technique towards disease targets of (2) retinal capillary non- perfusion in diabetic retinopathy and (3) choroidal neovascularization (CNV) in age-related macular degeneration (AMD). The visualization capabilities of PC-OCT imaging will be compared directly against fluorescein angiography images for subjects of the target diseases. Successful completion of the Phase I aims will lead to further development of PC-OCT imaging techniques and analysis for detection of vascular leakage and screening for sub-clinical CNV in asymptomatic fellow eyes. Developing motion contrast capabilities of PC-OCT to be used with clinically available SDOCT systems can establish a new non-invasive screening tool for retinovascular diagnosis. Earlier detection through non-invasive screening of AMD patients may enable earlier detection of subclinical CNV and initiation of therapy before central vision is lost. PUBLIC HEALTH RELEVANCE: This proposal describes a new software product that enhances the diagnostic capability of optical coherence tomography (OCT), the most commonly performed retinal diagnostic test used in the US for evaluation of macular degeneration and diabetic retinopathy. By non-invasively providing high resolution retinovascular imaging, the product, phase contrast OCT (PC-OCT), may potentially replace fluorescein angiography, the current invasive and costly gold standard for retinovascular imaging. The proposed research plan improves the capabilities of PC-OCT and then does a head-to-head comparison with fluorescein angiography in evaluation of patients with wet macular degeneration and diabetic retinopathy.